Animal, fungal and marine sources of cgp and increased cgp concentration for disease management and for treatment of non-neurological and/or neurological conditions

Abstract

Described herein are improvements relating to IGF-1 function analysis, adjustment and its application in disease management of non-neurological and/or neurological conditions. More specifically, methods relating to the clinical application of cyclic glycine-proline (cGP) and/or cGP/IGF-1 molar ratio as the plasma biomarker for prediction of risk and recovery of non-neurological and/or neurological conditions with IGF-1 dysfunction and the use of a cGP containing animal, marine or fungal based material such as concentrate/extract of hydrolysed bovine collagen and marine collagen, mushroom and seaweed along with plant-based cGPMAX™ for the treatment of same. The methods more accurately measure IGF-1 function in vivo indirectly using cGP and cGP/IGF-1 molar ratio along with a means to adjust and normalise cGP and cGP/IGF-1 molar ratio (and hence active IGF-1 concentration), and specific treatment methods for individuals with a lower or reduction of cGP level relative to a standard set of baseline data. Supplementation of bovine collagen formulated cGPMAX™ effectively improved the sensory function in patients with diabetic neuropathy.

What is claimed is: 
     
         1 . A method of treating non-neurological and/or neurological conditions associated with IGF-1 dysfunction in an animal comprising the steps of:
 a) obtaining a biological specimen from the animal;   b) measuring a concentration of cyclic glycine-proline (cGP) as a plasma biomarker for active concentration dependent insulin-like growth factor 1 (IGF-1) bioavailability in the biological specimen;   c) comparing either the measured cGP concentration and/or molar ratio of cGP concentration to total measured amount of IGF-1 in the biological specimen to a standard to confirm whether or not, in a continuum of results, the measured cGP concentration and/or ratio of cGP concentration to total measured amount of IGF-1 conforms to the relative standard for estimating IGF-1 function of the individual; and   d) administering a therapeutically effective amount of a concentrate/extract of derived from animal, marine and/or fungal based material to the animal to:   prevent a decrease in concentration of cGP and/or cGP to total measured IGF-1 molar ratio in an animal;   and/or maintain a pre-existing concentration of cGP and/or cGP to total measured IGF-1 molar ratio in an animal; and/or   increase the concentration of cGP and/or cGP to total measured IGF-1 molar ratio in an animal.   
     
     
         2 . A method of predicting a risk of a non-neurological and/or neurological condition with age in an animal utilising cyclic glycine-proline (cGP) as a plasma biomarker with altered IGF-1 function comprising the steps of:
 a) obtaining a biological specimen from the animal;   b) measuring a concentration of cyclic glycine-proline (cGP) as a plasma biomarker for active concentration dependent insulin-like growth factor 1 (IGF-1) bioavailability in the biological specimen at a first set age of the animal, or an initial stage of the non-neurological and/or neurological condition, or before treatment of an therapeutically effective amount of a concentrate/extract of cGP derived from animal, marine and/or fungal based material to the animal;   c) re-measuring the concentration of cyclic glycine-proline (cGP) plasma biomarker for active concentration dependent insulin-like growth factor 1 (IGF-1) bioavailability in the biological specimen at further set age intervals of the animal or further stage of the non-neurological and/or neurological condition, or after treatment of the therapeutically effective amount of the concentrate/extract of cGP derived from animal, marine and/or fungal based material to the animal; and   d) comparing either the measured cGP concentration and/or molar ratio of cGP concentration to total measured amount of IGF-1 in the biological specimen at the set age intervals relative to the first set age, or the initial stage of the non-neurological and/or neurological condition with IGF-1 dysfunction, or before the treatment of the therapeutically effective amount of a concentrate/extract of the cGP derived from animal, marine and/or fungal based material to the animal, in a continuum of results, to confirm whether or not there is a change in the measured cGP concentration and/or molar ratio of cGP concentration to total measured amount of IGF-1 thereby determining whether the animal is at an increased risk of developing a non-neurological and/or neurological condition from cognitive decline relative to a standard set of baseline data, and wherein the above measured ratio is used to select individual patients for cGP treatment and a suitable dosage for the cGP treatment therein.   
     
     
         3 . A method of predicting the spontaneous recovery of an animal with a non-neurological and/or neurological conditions with IGF-1 dysfunction utilising cyclic glycine-proline (cGP) and cGP/IGF-1 molar ratio as the plasma biomarker for IGF-1 function comprising the steps of:
 a) obtaining a biological specimen from the animal;   b) measuring a concentration of cyclic glycine-proline (cGP) plasma biomarker and active concentration dependent insulin-like growth factor 1 (IGF-1) bioavailability in the biological specimen at a baseline of the animal from onset of the non-neurological and/or neurological condition (<72 h in acute conditions);   c) re-measuring the concentration of cyclic glycine-proline (cGP) plasma biomarker and active concentration dependent insulin-like growth factor 1 (IGF-1) bioavailability in the biological specimen at further regular intervals of the animal during recovery;   d) evaluating functional recovery of the animal from the baseline and at further set intervals, and wherein the baseline concentration of CGP from a continuum of data predicts the short term outcome of non-neurological and/or neurological condition recovery of the animal such that a greater baseline cGP concentration, the more positive prognosis for the animal based on the evaluation of functional recovery.   
     
     
         4 . The use of a concentrate/extract of cGP derived from animal, marine and/or fungal based material in the manufacture of a medicament formulated to:
 prevent a decrease in concentration of cGP and/or cGP to total measured IGF-1 molar ratio in an animal; and/or   maintain a pre-existing concentration of cGP and/or cGP to total measured IGF-1 molar ratio in an animal; and/or   increase the concentration of cGP and/or cGP to total measured IGF-1 ratio in an animal.   
     
     
         5 . The use of a concentrate/extract of cGP derived from animal, marine and/or fungal based material in the manufacture of a medicament formulated for oral administration to ameliorate the effects of and/or treat non-neurological and/or neurological conditions in a patient in need thereof. 
     
     
         6 . A concentrate/extract comprising a therapeutically effective amount of cGP derived from animal, marine and/or fungal based material formulated for administration to an animal to:
 prevent a decrease in concentration of cGP and/or cGP to total measured IGF-1 molar ratio in an animal; and/or   maintain a pre-existing (normal/physiological) concentration of cGP and/or cGP to total measured IGF-1 molar ratio in an animal; and/or   increase or to normalise the concentration of cGP and/or cGP to total measured IGF-1 molar ratio in an animal.   
     
     
         7 . A method for ameliorating the effects of hypertension and/or a stroke; and/or treating hypertension and/or stroke; and/or reducing the symptoms associated with hypertension and/or stroke in a patient in need thereof, wherein the method comprises administering a therapeutically effective amount of a concentrate/extract of cGP derived from animal, marine and/or fungal based material. 
     
     
         8 . A method for ameliorating the effects of and/or treating Parkinson's disease or the symptoms associated with Parkinson's disease, or complications associated with cognitive impairment in a patient in need thereof, wherein the method comprises administering a therapeutically effective amount of a concentrate/extract of cGP derived from animal, marine and/or fungal based material. 
     
     
         9 . The method as claimed in any one of  claims 1 to 3 , wherein the non-neurological and/or neurological conditions or diseases are a Cerebrovascular accident or stroke, Mild Cognitive Impairment (MCI), Alzheimer's, vascular dementia, Rett syndrome, concussion, hypertension and its associated brain complications, Parkinson's and/or any other ageing related conditions or IGF-1 deficiency related conditions. 
     
     
         10 . The method as claimed in any one of  claims 1 to 3 , wherein administration halts a decrease in cGP concentration as a result of a disease or condition. 
     
     
         11 . The method as claimed in any one of  claims 1 to 3 , wherein administration increases cGP concentration by at least 1% above what would be measured in the patient with no cGP extract administration. 
     
     
         12 . The method as claimed in any one of  claims 1 to 3 , wherein the animal is human. 
     
     
         13 . The method as claimed in any one of  claims 1 to 3 , wherein the animal is healthy. 
     
     
         14 . The method as claimed in any one of  claims 1 to 3 , wherein the animal has a pre-existing condition or disease state. 
     
     
         15 . The method as claimed in any one of  claims 1 to 3 , wherein a standard or baseline is based on a set of data collected for a patient. 
     
     
         16 . The method as claimed in any one of  claims 1 to 3 , wherein the standard or baseline is based on a set of data collected for a population. 
     
     
         17 . The method as claimed in any one of  claims 1 to 3 , wherein the medicament is formulated for oral administration. 
     
     
         18 . The method as claimed in any one of  claims 1 to 3 , wherein the medicament is formulated for parenteral administration. 
     
     
         19 . The method as claimed in any one of  claims 1 to 3 , wherein the medicament is formulated as a pill, tablet, capsule, liquid, powder, micronized powder, gel, soft gel full of liquid and/or combinations thereof. 
     
     
         20 . The method as claimed in  claim 19 , wherein the micronized powder particle sizes substantially between 1 to 1000 micron. 
     
     
         21 . The method as claimed in any one of  claims 1 to 3 , wherein the medicament is administered to provide a therapeutically effective dose of concentrated cGP of at least between 10,000 to 100,000 ng (10-100 μg) as daily dose. 
     
     
         22 . The method as claimed in any one of  claims 1 to 3 , wherein there is at least a 25% increase of cGP in the cerebrospinal fluid (CSF) after cGP extract supplementation. 
     
     
         23 . The concentrate/extract as claimed in any one of  claims 4 to 6 , wherein the concentrate/extract with high concentration of cGP is derived from any animal, marine and/or fungal sources including any living organism selected from any of bovine, marine and bone collagen sources. 
     
     
         24 . The concentrate/extract as claimed in any one of  claims 4 to 6 , wherein a hydrolysation process of the extract cleaves collagen/gelatine proteins and forms linear peptides with repeated sequences of hydrolysed proline-glycine, wherein cyclisation of these linear peptides leads to production of cGP to normalise IGF-1 function. 
     
     
         25 . The concentrate/extract as a claimed in  claim 23 , wherein the concentrate/extract is hydrolysed bovine collagen powder, collagen marine skin powder, hydrolysed fish skin powder and/or bone collagen. 
     
     
         26 . The concentrate/extract as claimed in any one of  claims 4 to 6 , wherein the concentrate/extract is processed and produced using body parts selected from: skins, proteins, bones, muscles tendons and the like and/or combinations thereof. 
     
     
         27 . The concentrate/extract as claimed in  claim 26 , wherein the concentrate/extract is produced by maceration of animal, marine and/or fungal material, followed by drying to form a concentrated powder that is micronized. 
     
     
         28 . The concentrate/extract as claimed in  claim 27 , wherein the micronized powder is encapsulated within soft gels and/or hard shells. 
     
     
         29 . The extract as claimed in any one of  claims 4 to 6 , wherein the concentrate/extract blend comprises Cyclic glycine-proline (cGP) in a concentration to provide at least 10,000 ng or more as a daily dose. 
     
     
         30 . The concentrate/extract as claimed in any one of  claims 4 to 6 , wherein the concentrate/extract, either in combination or separately is attributed to the observed effect in vivo on the binding of IGF-1 and the observed increase in cGP concentration and/or cGP to total IGF-1 ratio. 
     
     
         31 . The concentrate/extract as claimed in any one of  claims 4 to 6 , wherein the concentrate/extract comprises other bioactive compounds besides cGP. 
     
     
         32 . The concentrate/extract as claimed in any one of  claims 4 to 6 , wherein, collagen and gelatine (the heated form of collagen) is high in glycine-hydroxyproline amino acid sequences and wherein the breakdown of collagen/gelatine forms a significant amount of cGP. 
     
     
         33 . The concentrate/extract as claimed in  claim 32 , wherein formation of cGP from gelatine breakdown is dependent on lower pH and higher temperature. 
     
     
         34 . The concentrate/extract as claimed in  claim 32 or claim 33 , wherein, an increase of cGP concentration following capsulisation in soft gel capsules is from 0.1 ng/mg to 10 ng/mg. 
     
     
         35 . The concentrate/extract as claimed in any one of  claims 32 to 34 , wherein incubated concentrate with collagen at 350 C for two weeks increases the cGP concentration from 40 ng/mg to 120 ng/mg. 
     
     
         36 . A soft gel or hard shell capsule used to encapsulate cGP extracted material for administration thereof, and wherein the cGP concentration of the extracted material contained therein increases over a period of time.